Definition

An orally available inhibitor of dihydroorotate dehydrogenase (DHODH), with potential antineoplastic, anti-inflammatory and antiviral activities. Upon oral administration, DHODH inhibitor RP7214 specifically targets, binds to and prevents the activation of DHODH, thereby preventing the fourth enzymatic step in de novo pyrimidine synthesis. This prevents uridine monophosphate (UMP) formation, DNA synthesis, cell division and cellular proliferation, promotes cell differentiation, causes cell cycle arrest and induces apoptosis in susceptible tumor cells. In addition, by preventing DHODH activity in host cells, RP7214 may reduce the ability of certain viruses, such as SARS-CoV-2, to replicate, thereby reducing viral load and infection. Also, by preventing pyrimidine synthesis, RP7214 causes anti-inflammatory and immunomodulatory effects by decreasing the activation and expansion of pro-inflammatory Th1 effectors and promoting the differentiation of immunomodulatory Th2 cells, and decreasing the production of various pro-inflammatory cytokines. RP7214 could potentially attenuate the excessive production of inflammatory cytokines and the cytokine-mediated inflammatory symptoms, which are seen in certain viral infections. DHODH, a mitochondrial enzyme, catalyzes the conversion of dihydroorotate (DHO) to orotate in the endogenous synthesis of UMP.